The purpose of this investigation was to determine the effectiveness of a Hospital to Home (H2H) nutrition management model on the postoperative clinical outcomes of patients with laryngeal carcinoma. Eighty-six patients with laryngeal carcinoma were randomly divided into an observation (H2H nutrition management) or control group (routine nutrition management). The ratios of urine lactulose to mannitol (L/M) in serum orexin-A levels of patients in both groups on the 1st postoperative day were significantly higher than before surgery; these levels decreased from the 7th and 14th postoperative day, but remained higher than before surgery (p<0...

Behavioral studies have suggested that (p-ClPhSe)2 elicits an anorectic-like action in rats by inducing multiple effects such as satiety-enhancing effect, malaise and specific flavor; however, the molecular mechanisms underlying its anorexigenic action remain unclarified. Here, male Sprague-Dawley rats received acute and sub-chronic intraperitoneal treatments with (p-ClPhSe)2; thereafter, in vivo and ex vivo analyses were carried out. The present study reveals that the reduction of food intake resulting from a single treatment with (p-ClPhSe)2 (1mg/kg, i...

Narcolepsy type 1 (NT1) is a rare sleep disorder caused by the very specific loss of hypothalamic hypocretin (Hcrt)/orexin neurons. The exact underlying process leading to this destruction is yet unknown, but indirect evidence strongly supports an autoimmune origin. The association with immune-related genetic factors, in particular the strongest association ever reported in a disease with an allele of a human leukocyte antigen (HLA) gene, and with environmental factors (i.e., the H1N1 influenza infection and vaccination during the pandemic in 2009) are in favor of such a hypothesis...

The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1...

The present study describes the nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of the springhare and Beecroft's scaly-tailed squirrel following immunohistochemical labelling. We aimed to investigate any differences in the nuclear organization of these neural systems when compared to previous data on other species of rodents, as these two rodent species have relatively large brains - 1.2 to 1.4 times larger than would be expected for mammals of their body mass and 1...

Purpose: The neuropeptides orexin-A and orexin-B are widely expressed in the vertebrate retina; however, their role in visual function is unclear. This study investigates whether and how orexins modulate signal transmission to dopaminergic amacrine cells (DACs) from both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (melanopsin-expressing intrinsically photosensitive retinal ganglion cells [ipRGCs]). Methods: A whole-cell voltage-clamp technique was used to record light-induced responses from genetically labeled DACs in flat-mount mouse retinas...

The orexins are hypothalamic neuropeptides and their role in reward processing and drug addiction has been demonstrated. The extent of involvement of each orexin receptor in the acquisition and expression of conditioned place preference (CPP) for morphine is still a matter of controversy. We investigated the functional differences between orexin-1 and -2 receptor blockade in the ventral tegmental area (VTA) on the acquisition and expression of morphine CPP. A total of 86 adult male Wistar rats weighing 250±30g (age 7-8weeks) received intra-VTA microinjection of either SB334867 (0...

Orexin receptor shave essential role in the induction of reward-related behaviors to several drugs of abuse. In the present study, we investigated the effects of bilateral administration of SB334867, as an orexin-1 receptor antagonist, and TCS OX2 29, as an orexin-2 receptor antagonist, into the nucleus accumbens (NAc) on the acquisition of morphine-induced conditioned place preference (CPP) in the rats. Adult male Wistar rats (n=80; 220-250g) were entered in a CPP paradigm. Bilateral microinjections of different doses of SB334867 (1, 3, 10 and 30nM) or TCS OX2 29 (3, 10, 30 and 100nM) into the NAc (0...

Prolonged use/abuse of opioid agonists leads to development of severe dependence to these drugs. Orexin-A has a crucial role in development of morphine dependence. The locus coeruleus (LC) is implicated in the expression of morphine withdrawal signs. Hyperactivity of LC neurons as well as increased intracellular cyclic adenosine monophosphate (cAMP) level temporally corresponds to the expression of opioid withdrawal behaviors. In this study the effect of central OX1R blockade on neuronal activity and cAMP content of LC neurons was investigated following naloxone administration in morphine-dependent rats...

Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors...

BACKGROUND: Long-term potentiation (LTP) is well recognized as a cellular-correlated synaptic plasticity of learning and memory. However, its reversal forms of synaptic plasticity, depotentiation, is less studied and its association with behaviors is also far from clear. Previously, we have shown that nanomolar orexin A can prevent the depotentiation induced by low frequency stimulation (LFS) following theta burst stimulation-induced LTP, namely inducing re-potentiation, at hippocampal CA1 synapses in vitro...

AIM: Accumulating evidence suggests that orexin signaling is involved in the regulation of blood pressure and cardiovascular function. However, the underlying mechanisms are not clear. Here we test the hypothesis that upregulated orexin A signaling in the paraventricular nucleus (PVN) increases sympathetic nerve activity (SNA) through stimulating expression of proinflammatory cytokines (PICs). METHODS: In vivo sympathetic nerve recordings were performed to test the impact of PVN orexin signaling on sympathetic outflow in Sprague-Dawley (SD) rats...

Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks...

Neuropeptides orexin-A and -B are related to the regulation of sleep/wakefulness and feeding behaviors. Recently, the peptides have also been shown to yield antinociceptive effects in various pain models. However, it is not clear whether orexins are involved in forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), the increase and the decrease of synaptic efficacy, respectively. In the present study, we examined whether orexin receptor type 1 (OX1) and 2 (OX2) are involved in the induction or maintenance of LTD of excitatory synaptic transmission using transverse spinal cord slices of young rats...

Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations...

Orexin-A and -B neuropeptides are exclusively synthesized in hypothalamic neurons. These have been implicated to play critical roles in the expression of various behavioral manifestations such as feeding, arousal, wakefulness, drug dependence and tolerance. Orexin ligands activate orexin type-1 and orexin type-2 receptors each displaying a distinct selectivity and distribution profile. Orexinergic neurons innervate various brain structures among which the locus coeruleus (LC) and the lateral paragigantocellularis (LPGi) nuclei are well established as the two key mediators of opiate dependence and tolerance...

The design, synthesis, and structure activity relationships of the novel class of pyrazolylethylbenzamide orexin receptor 1-selective antagonists are described. Further derivatization of the prototype dual orexin receptor 1/2 antagonist lead (1) by installing a (S)-methyl group into the ethyl linker moiety between the pyrazole ring and benzamide resulted in an increase of the antagonist potency against orexin receptor 1/2 receptors. Optimization of the benzamide and pyrazole parts of compounds 2 and 9b led to the identification of N-ethyl-5-fluoro-N-{(2S)-1-[5-(4-fluorophenyl)-2H-tetrazol-2-yl]propan-2-yl}-2-(pyrimidin-2-yl)benzamide (24), which exhibited excellent antagonistic activity against orexin receptor 1 with an IC50 of 2...

Insomnia is a condition with sleep problems and many people suffered from it. Chronic insomnia can last for long time and it will severely affect people's health and the quality of life. In conventional medicine, the most commonly used the medicine is benzodiazepine. It is effective but also has significant side effects. Patients try to use some kinds of alternative medicines. Chinese medicinal herbs and formulas have been used in the treatment of insomnia for more than 2000 years in China. In recent decades, Chinese herbal medicine has been widely used in the Western countries...